BOSTON — An investigational catheter lock solution (CLS) significantly decreased catheter-related bloodstream infections among end-stage renal disease (ESRD) patients with hemodialysis through a central venous catheter (CVC), according to researchers here.
Compared with heparin, CRMD003 (Neutrolin) lowered the risk of catheter-related bloodstream infections (CRBSI) by 71% (P=0.0006), reported Anil Agarwal, MD, of The Ohio State University College of Medicine in Columbus, and colleagues.
The Data and Safety Monitoring Board suggested terminating the LOCK-IT-100 trial early based on efficacy after a pre-specified interim analysis, Agarwal said at the National Kidney Foundation (NKF) Spring Clinical Meeting.
CRMD003 (taurolidine 1.35%, citrate 3.5%, and heparin 1,000 U/mL or TCH) has broad antibacterial and antifungal activity, and no reported microbial resistance in humans. The agent is approved in the EU for the prevention of CRBSI, and has been given Fast Track Designation, as well as Qualified Infectious Disease Product Designation, by the FDA.
“Infections are the second leading cause of death in hemodialysis patients. Hemodialysis [HD] patients are at risk for bloodstream and vascular access infections due to immuno-compromised status and frequent vascular access,” Agarwal said.
CVCs comprise a small proportion of all dialysis vascular accesses, yet they account for the majority of all access-related bloodstream infections. Bloodstream infection-related hospitalizations are quite expensive for each episode, and the cost tends to increase for cases of metastatic infection like endocarditis, Agarwal highlighted.
Prior research has shown that the decreased CRBSI in hemodialysis patients versus recent CRBSI rates in these patients. Other research has shown that compared with historical heparin, TCH has lowered staph bacteremia and all-cause bacteremia, he noted.
CRBSI are a concern with dialysis catheters, noted NKF session chair Joseph Vassalotti, MD, of the National Kidney Foundation in New York City. “Preliminary data were presented here, so I certainly want to see full publication and more granular presentation.”
“With the NKF’s KDOQI vascular access guideline, that’s going to be published soon, we are going to get a sense of individualized care for the patients,” Vassalotti told MedPage Today. For some patients, unfortunately, catheters are here to stay. We like to try to avoid them if we can, but there are going to be some patients that are going to need them. This is an exciting opportunity, perhaps, to mitigate the risk of catheter-related bloodstream infection.”
For the phase III, prospective, multicenter, double-blind randomized, active control trial, Agarwal’s group randomized hemodialysis patients using tunneled dialysis catheter 1:1 to the heparin group (n=398) and to the CRMD003 (n=397) group.
Inclusion criteria were:
- CVC use for a minimum of 60 days going forward
- A minimum life expectancy of 180 days
- Single pool peritoneal dialysis and hemodialysis therapy adequacy*time/Volume (Kt/V) over 1.2 over the last month
- HD catheter flow of a minimum of 250 mL/min
- Women capable of childbearing with reliable contraception and a negative pregnancy test
- ESRD with HD at least two times per week
- Subclavian site or internal jugular with tip in right atrium-superior vena cava junction
Some of the exclusion criteria included active malignancy, open, non-healing ulcers, compromised catheter exit site, immunosuppression that raises infection risk, orv recombinant tissue plasminogen activator use within the previous 1 month with current catheter.
For authors reported the following for CRMD003 and heparin, respectively:
- Loss of catheter patency: 0.99 per 1,000 catheter days (CD) and 0.74 per 1,000 CD (P=0.12)
- Catheter removal for any reason: 3.48 per 1,000 CD and 3.23 per 1,000 CD (P=0.416)
- Catheter removal for positive reasons: 2.39 per 1,000 CD (95% CI 2.05-2.79) and 1.90 per 1,000 CD (95% CI 1.60-2.25)
- Catheter removal for negative events: 1.09 per 1,000 CD (95% CI 0.87-1.37) and 1.34 per 1,000 CD (95% CI 1.09-1.64)
- Treat-emergent adverse events: 5.8 and 5.1 per patient
However, treatment-emergent serious adverse events (device-related infection, pneumonia, and acute MI, to name a few) were similar between both arms and were infrequent at ≤2%, the authors reported.
Agarwal disclosed relevant relationships with CorMedix. Some co-authors are CorMedix employees. Other co-authors disclosed multiple relevant relationships with industry including CorMedix.